Water‐Soluble Maleimide‐Modified Gold Nanoparticles (AuNPs) as a Platform for Cycloaddition Reactions

Abstract

Maleimide‐terminated triethylene glycol thiolate monolayer‐protected gold nanoparticles (Mal‐EG4‐AuNPs) with a core size of 2.5 ± 0.7 nm were prepared. Mal‐EG4‐AuNPs were modified in high yields via interfacial 1,3‐dipolar cycloaddition and Diels–Alder reactions with a variety of nitrones and dienes, respectively. The resulting cycloadduct‐modified AuNPs were characterized using 1H NMR spectroscopy and were verified by comparison of the spectra to those of the products of the model reactions with the same nitrones and dienes. TEM analysis showed that the reaction conditions did not affect the shape or size of the gold core, suggesting that this is an efficient methodology to modify small water soluble AuNPs under ambient pressure and biological temperature with high yields and a reasonable reaction time.

Bioorthogonal Reactions Utilizing Nitrones as Versatile Dipoles in Cycloaddition Reactions

“…Through hydrogen bonds formed within the complex, the LUMO energy of the alkene was lowered and the rate of the reaction was accelerated 5-fold in CDCl 3 at 10 °C. , Another method to overcome the inefficiency of this reaction was demonstrated by Workentin et al., who used high-pressure conditions to synthesize isoxazolidine-tethered monolayer-protected nanoparticles. The authors showed that hyperbaric conditions (11,000 atm) decreased the reaction times of these reactions from averaging 10 h to 2 weeks at 1 atm to 10–60 min at 11,000 atm …”

Maleimide-Modified Gold Nanoparticles (AuNPs): A Versatile ­Platform for Interfacial Click Reactions Leading to Chemically Modified AuNPs

“…However, nitrones or dienes with bulky substituents were still found to react on the timescale of days, suggesting that for these two types of reactions steric restrictions represent the main rate-limiting factor. 28 The major improvement was observed for the Michael-type addition reaction, the reaction time of which in protic solvents decreased from days to minutes or hours. This opened a plethora of new possibilities and applications for the maleimide-AuNP template.…”

Exploiting Double Exchange Diels-Alder Cycloadditions for Immobilization of Peptide Nucleic Acids on Gold Nanoparticles

“…In this context, bio-conjugation of nanomaterials, often exploits these approaches because of the tolerance of aqueous solutions and the high reaction selectivity (Sapsford et al, 2013). Diels-Alder-based approaches were previously exploited in NP context as a means to protect maleimide-containing thiols prior to their surface decoration, for the realization of NP-NP dimers, for biopolymer NP functionalization with antibodies and in stimuli-responsive drug release systems (Zhu et al, 2006;Liu et al, 2010;Ghiassian et al, 2015;Oluwasanmi et al, 2017).…”